Synthesis of glycosylphosphatidylinositol (GPI) Authored: D'Eustachio, P, 2005-04-04 21:01:34 Edited: D'Eustachio, P, 0000-00-00 00:00:00 GENE ONTOLOGYGO:0016254 Glycosylphosphatidyl inositol (GPI) acts as a membrane anchor for many cell surface proteins. GPI is synthesized in the endoplasmic reticulum. In humans, a single pathway consisting of nine reactions appears to be responsible for the synthesis of the major GPI species involved in membrane protein anchoring. This pathway is shown in the figure. Two additional reactions, not shown, allow the synthesis of variant forms of GPI, one with an additional mannose residue and one with an additional ethanolamine (Tauron et al. 2004; Shishioh et al. 2005). These variant GPI molecules may be used for tissue-specific protein modifications, or may function independently.<p>The steps of GPI synthesis were first identified by isolating large numbers of mutant cell lines that had lost the ability to express GPI anchored proteins on their surfaces. Somatic cell hybrid analyses of these lines allowed the definition of complementation groups corresponding to distinct mutated genes, and cDNAs corresponding to normal forms of these genes were identified on the basis of their abilities to restore normal cell surface protein expression in mutant cells. Co-precipitation experiments with tagged cloned proteins have allowed the identification of additional proteins involved in GPI anchor biosynthesis. Pubmed11102867 Pubmed15208306 Pubmed15632136 Reactome Database ID Release 43162710 Reactome, http://www.reactome.org ReactomeREACT_952 Reviewed: Orlean, P, 0000-00-00 00:00:00 PathwayStep3092 PathwayStep3091 PathwayStep3093 PathwayStep3090 PathwayStep3089 PathwayStep3088 PathwayStep3087 PathwayStep3086 PathwayStep3085 PathwayStep3084 PathwayStep3083 glucosaminyl-acyl-PI + dolichol phosphate D-mannose -> mannose(al1-4)glucosaminyl-acyl-PI + dolichol phosphate glucosaminyl-PI + fatty acyl-CoA -> glucosaminyl-acyl-PI + CoA-SH Reorientation of glucosaminyl-acyl-PI in the endoplasmic reticulum membrane N-acetylglucosaminyl-PI + H2O -> glucosaminyl-PI + acetate mannose(a1-4)glucosaminyl-acyl-PI + phosphatidylethanolamine -> (ethanolamineP) mannose(al1-4)glucosaminyl-acyl-PI + diacylglycerol phosphatidylinositol + UDP-N-acetyl-D-glucosamine -> N-acetylglucosaminyl-PI + UDP (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PI + dolichol phosphate D-mannose -> mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PI + dolichol phosphate mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PI + dolichol phosphate D-mannose -> mannose (a1-2) mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PI + dolichol phosphate mannose (a1-2) mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PI + phosphatidylethanolamine -> (ethanolamineP) mannose (a1-2) mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PI (acyl-GPI) + diacylglycerol mannose (a1-2) mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PI -> mannose (a1) mannose (a1-2) mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PI (ethanolamineP) mannose (a1-2) mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PI -> (ethanolamineP) mannose (a1-2) (ethanolamineP) mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PI